Analysis of CD20 and PD-L1 levels on small extracellular vesicles (sEV) produced by DLBCL cells and EBV-transformed B cells, and potential role in T cell inhibition.

Autor: Akil H; CRIBL, UMR CNRS 7276 -INSERM U1262, CBRS, Université de Limoges, 2 Rue du Docteur Marcland, 87025, Limoges Cedex, France., Bentayeb H; CAPTuR UMR INSERM U1308, Facultés de Médecine et de Pharmacie, Université de Limoges, 2 Rue du Docteur Marcland, 87025, Limoges Cedex, France., Aitamer M; CRIBL, UMR CNRS 7276 -INSERM U1262, CBRS, Université de Limoges, 2 Rue du Docteur Marcland, 87025, Limoges Cedex, France., Vignoles C; CRIBL, UMR CNRS 7276 -INSERM U1262, CBRS, Université de Limoges, 2 Rue du Docteur Marcland, 87025, Limoges Cedex, France., Abraham J; CRIBL, UMR CNRS 7276 -INSERM U1262, CBRS, Université de Limoges, 2 Rue du Docteur Marcland, 87025, Limoges Cedex, France.; Service d'Hématologie Clinique, CHU de Limoges, 2 Avenue Martin Luther King, 87000, Limoges, France., Gachard N; CRIBL, UMR CNRS 7276 -INSERM U1262, CBRS, Université de Limoges, 2 Rue du Docteur Marcland, 87025, Limoges Cedex, France.; Laboratoire d'hématologie, CHU de Limoges, 2 Avenue Martin Luther King, 87000, Limoges, France., Olivrie A; Service d'Hématologie Clinique, CHU de Limoges, 2 Avenue Martin Luther King, 87000, Limoges, France., Guyot A; Service d'Anatomie Pathologique, CHU de Limoges, 2 Avenue Martin Luther King, 87000, Limoges, France., Gobbo J; INSERM 1231, Label Ligue National Contre le Cancer and Label d'excellence LipSTIC of Dijon; Early Phase Unit INCa CLIP, Anti-Cancer Center Georges-François Leclerc, Dijon, France., Feuillard J; CRIBL, UMR CNRS 7276 -INSERM U1262, CBRS, Université de Limoges, 2 Rue du Docteur Marcland, 87025, Limoges Cedex, France.; Laboratoire d'hématologie, CHU de Limoges, 2 Avenue Martin Luther King, 87000, Limoges, France., Shirvani H; Institut Roche, 30, Cours de L'île Seguin, 92650, Boulogne-Billancourt, France., Troutaud D; CRIBL, UMR CNRS 7276 -INSERM U1262, CBRS, Université de Limoges, 2 Rue du Docteur Marcland, 87025, Limoges Cedex, France. danielle.troutaud@unilim.fr.
Jazyk: angličtina
Zdroj: Experimental hematology & oncology [Exp Hematol Oncol] 2024 May 17; Vol. 13 (1), pp. 53. Date of Electronic Publication: 2024 May 17.
DOI: 10.1186/s40164-024-00518-2
Abstrakt: Increasing evidence supports a role for small extracellular vesicles (sEV, including exosomes) in Diffuse Large B-cell lymphoma (DLBCL) progression and resistance to treatment. CD20 and PD-L1 are found on DLBCL-derived sEV, but little is known about their patient-level heterogeneity. Moreover, the capacity of PD-L1 + sEV to modulate T cells needs to be clarified. Herein we analyzed sEV produced by human DLBCL cell lines and EBV-transformed B cell-lymphoblastoid cell lines (LCLs), a model allowing autologous T cell co-cultures. We determined CD20 and PD-L1 levels on plasma sEV from patient samples vs healthy volunteers (HV). sEV functional relevance was also investigated on CD4 + and CD8 + T cells. sEV derived from all cell lines showed an enrichment of CD20 and a high glycosylated PD-L1 expression when compared to cell lysates. High PD-L1 expression on LCL-derived sEV was associated with higher CD4 + and CD8 + T cell apoptosis. In patients, plasma sEV concentration was higher vs HV. Compared to sEV-CD20 level that seemed higher in patients, PD-L1 level in sEV was not different from those of HV. A high glycosylated PD-L1 level was shown in sEV from both patients and HV plasma samples, that was associated with the same inhibiting effect on activated T cells. We conclude that sEV derived from EBV-transformed B cells realize an immunosuppressive role that involved cell-cell interaction and probably at least PD-L1. Furthermore, our findings suggest the potential of circulating sEV as a source of biomarkers in DLBCL, notably to have information on immunotherapeutic target levels of parental tumor cells.
(© 2024. The Author(s).)
Databáze: MEDLINE
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